P1345: IMMUNE RECONSTITUTION AFTER BMT FOR NON-MALIGNANT HEMATOLOGICAL CONDITIONS FOR RELATED, UNRELATED AND HAPLOIDENTICAL DONORS. A STUDY IN THE PEDIATRIC DEPARTMENT AT ST MARY’S HOSPITAL BETWEEN 2019&amp;2020
Authors: A. Khoder, A. Gassas, S. Bremathas, O. Rabanal, K. Hennesy, S. Loaiza, K. Lund, T. Petterson, L. Karnik, J. Josu de la Fuente
Journal: HemaSphere (2022)

Background: Allogeneic blood & marrow transplant (BMT) is a curative option for a wide range of non-malignant childhood hematological conditions. Significant comorbidity and mortality is associated with delayed immune reconstitution (IR). Previous studies on the main included patients with malignant conditions with previous exposure to chemotherapy and different kinetics of chimerism are likely to have an impact on IR Aims: To study IR in a single pediatric BMT Center, St Mary’s Hospital, Imperial College London between 2019 and 2020, which exclusively undertakes BMT for non-malignant hematological conditions (hemoglobinopathies and bone marrow failure) comparing matched sibling (Sib), haploidentical (Haplo) and matched unrelated donor (MUD Methods: Peripheral blood was collected monthly for lymphocyte subsets: CD4+, CD8+,CD56+,CD19+ cells and IgG, IgA and IgM levels in 49 consecutive patients. IR is defined as median cell count reaching ≥ lower normal limit or > a cut-off of clinical significance e.g CD4+ cell>300/μL. Conditioning regimens varied per indication, donor source and degree of HLA matching but were maintained consistently throughout the study period. Thymoglobulin (rabbit ATG, Genzyme, dose range 4.5 -11.25 mg/kg) was the T cell depletion used in all conditioning regimens except for Fanconi anaemia (FA), where alemtuzumab 0.3 and 0.9 mg/kg was used for Sib and unrelated transplantation, respectively. Thymoglobulin stopped on day -2 except in Haplo was given upfront and alemtuzumab on day -4. TBI 2-3 Gy was incorporated in conditioning for mismatched unrelated BMT for FA and in all haplo. Haplo BMT was performed with PTCy. Results: Type of BMT was as follows: 44% Sib, 27% Haplo and 19% MUD; for following indications 37% sickle cell anaemia, 35% thalassaemia, 12% AA, 8% DBA, 6% FA and 2% DC. Median age was 8.5 y (3-19). Almost half the patients were ≤6 years at time of BMT with 3/49 ≥18 years. Any form of aGVHD occurred in 29%, 54% and 55% of Sib, Haplo and MUD, and cGVHD in 5%, 23% and 27%, respectively. Innate immunity CD56+NK and CD3+CD8+cytotoxic cells were first to reconstitute. Median CD56+cell count >100 (100-1200 /μL) in Sib and MUD were observed by 1st month while in Haplo in 2nd month post BMT. Median CD8+ >200 (200-1300/μL) was first observed 4 months post BMT in Sib and Haplo and 7 months in MUD. Adoptive immunity CD4+and CD19+cells expectedly took longer to reconstitute. Median CD4+count>300 (700-4000/μL) was noted at 7 months post BMT in Sib, and 8-10 months in MUD and Haplo. However, reaching lower normal limit was only achieved by end of 1st year for Sib and not reached in the Haplo at 12 months. Median CD19+B cell count reached >100 (100-1200/μL) at 2 to 4 months in Sib; continued to rise throughout first year, and 8 to 10 months in MUD while in Haplo, this was not reached by end of 1st year. IgG level remained >5 g/L throughout post BMT in Sib. Although B cell reconstitution was delayed, level remained >5 g/L throughout the 12 months post BMT in Haplo; this may reflect the use of IVIg treatment or replacement. In MUD, IgG levels were lower than other two cohorts at or close to 5 g/L most of the time. IgM and IgA levels have remained mostly below lower normal limit throughout the first-year post BM. Summary/Conclusion: IR for non-malignant hematological conditions in children is reached at different time point following BMT. Haplo is associated with delayed IR therefore poses higher risk of infection. Comprehensive phenotypic analysis of IR is required to help assess infection and risk and guide effective prophylaxis